U.S. patent application number 11/073095 was filed with the patent office on 2005-08-04 for high concentration dinotefuran formulations containing methoprene.
Invention is credited to Ahn, Albert, Cottrell, Ian William, Lytwyn, Michael William.
Application Number | 20050169954 11/073095 |
Document ID | / |
Family ID | 33415822 |
Filed Date | 2005-08-04 |
United States Patent
Application |
20050169954 |
Kind Code |
A1 |
Cottrell, Ian William ; et
al. |
August 4, 2005 |
High concentration dinotefuran formulations containing
methoprene
Abstract
A topical insecticide is provided which can be safe to use and
avoids many common deleterious side effects of conventional topical
insecticides. In one preferred embodiment of the invention, the
active ingredient of the insecticide formulation is an amine
derivative, having a nitro-methylene group, a nitroamino group or a
cyanoamino group, which can be formulated to have low toxicity and
excellent insecticidal activity. One particularly suitable
insecticide is 1-{(tetrahydro-3-furanyl)methyl}-2-n-
itro-3-methylguanidine (dinotefuran), an aldulticide that will kill
adult fleas combined with methoprene.
Inventors: |
Cottrell, Ian William;
(Basking Ridge, NJ) ; Lytwyn, Michael William;
(East Hanover, NJ) ; Ahn, Albert; (Short Hills,
NJ) |
Correspondence
Address: |
STROOCK & STROOCK & LAVAN LLP
180 MAIDEN LANE
NEW YORK
NY
10038
US
|
Family ID: |
33415822 |
Appl. No.: |
11/073095 |
Filed: |
March 4, 2005 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
11073095 |
Mar 4, 2005 |
|
|
|
10411720 |
Apr 11, 2003 |
|
|
|
6889632 |
|
|
|
|
10411720 |
Apr 11, 2003 |
|
|
|
10242550 |
Sep 12, 2002 |
|
|
|
6588374 |
|
|
|
|
10411720 |
Apr 11, 2003 |
|
|
|
10242551 |
Sep 12, 2002 |
|
|
|
6867223 |
|
|
|
|
10411720 |
Apr 11, 2003 |
|
|
|
10242552 |
Sep 12, 2002 |
|
|
|
6814030 |
|
|
|
|
Current U.S.
Class: |
424/405 |
Current CPC
Class: |
A01N 47/40 20130101;
A01N 43/08 20130101; A01N 43/08 20130101; A01N 51/00 20130101; A01N
51/00 20130101; A01N 47/40 20130101; A01N 51/00 20130101; A01N
2300/00 20130101; A01N 2300/00 20130101; A01N 49/00 20130101; A01N
43/40 20130101; A01N 2300/00 20130101; A01N 25/02 20130101 |
Class at
Publication: |
424/405 |
International
Class: |
A01N 025/00 |
Claims
What is claimed is:
1. An insecticide formulated by dissolving an insecticidably
effective amount of an insecticidal
(tetrahydro-3-furanyl)methylamine derivative in an effective amount
of a solvent component, said solvent component comprising
sufficient methoprene to increase the solvency of the insecticidal
derivative in the solvent component compared to the solvency of the
insecticidal derivative in the solvent component without the
methoprene and to increase the effectiveness of the insecticide
compared to its effectiveness without the methoprene.
2. The insecticide of claim 1, wherein said insecticidal derivative
is dinotefuran.
3. The insecticide of claim 2, wherein said solvent component
comprises phenyl methanol.
4. The insecticide of claim 1, wherein said insecticidal derivative
is dissolved in the formulation to a concentration of about 5 to
25%.
5. The insecticide of claim 3, wherein said insecticidal derivative
is dissolved in the formulation to a concentration of about 9 to
20%.
6. The insecticide of claim 5, comprising over 0.1% methoprene.
7. The insecticide of claim 5, comprising about 0.1 to 3%
methoprene.
8. The insecticide of claim 1, wherein the formulation is not
irritating to dogs or cats and is effective to kill fleas with
applications of less than 20 ml to a cat.
9. The insecticide of claim 2, wherein the formulation is not
irritating to dogs or cats and is effective to kill fleas with
applications of less than 20 ml to a cat.
10. The insecticide of claim 3, wherein the formulation is not
irritating to dogs or cats and is effective to kill fleas with
applications of less than 20 ml to a cat.
11. The insecticide of claim 1, wherein one drop of the formulation
is effective to kill fleas on a cat for at least one month.
12. The insecticide of claim 2, wherein one drop of the formulation
is effective to kill fleas on a cat for at least one month.
13. The insecticide of claim 3, wherein one drop of the formulation
is effective to kill fleas on a cat for at least one month.
14. A method of controlling insect infestation in animals,
comprising dissolving dinotefuran in a solvent mixture comprising
methoprene and applying an insecticidably effective amount of the
solution to an animal.
15. The method of claim 14, wherein the animal is a cat or a
dog.
16. The method of claim 15, wherein the insect is a flea.
17. A method of preparing an insecticide, comprising dissolving an
insecticide in a composition comprising methoprene, wherein at
least a portion of the insecticide is dissolved by the methoprene.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a continuation of U.S. Ser. No.
10/411,720, now allowed, filed Apr. 11, 2003 which is a
continuation-in-part of U.S. Ser. No. 10/242,550, now U.S. Pat. No.
6,588,374, U.S. Ser. No. 10/242,551, now allowed, and U.S. Ser. No.
10/242,552, now U.S. Pat. No. 6,814,030, all of which were filed
Sep. 12, 2002. Priority is claimed to all of the applications
listed above, which are incorporated herein by reference.
BACKGROUND OF INVENTION
[0002] The invention relates generally to insecticides and more
particularly to a topical insecticide, such as one suitable to use
on house pets such as cats and dogs.
[0003] The infestation of animals with fleas, ticks, flies and the
like is highly undesirable. Accordingly, it has become common to
administer both topical and internal insecticides to livestock and
pets. Topical applications can be desirable, in that many
insecticides are acceptably safe when used topically, but not when
used internally.
[0004] Various topical insecticides have drawbacks. Some require a
large volume to be applied to the animal. This can cause
considerable mess and can lead to an unpleasant smell. Also, when
the animal is a house pet, there is a further complication in that
the insecticide should be safe for human contact. It should also
not lead to staining of furniture, carpeting and the like. Finally,
even if safe, topical insecticides for house pets should not be
irritating or lead to rashes, hair loss or exhibit other unpleasant
side effects.
[0005] Accordingly, it is desirable to provide an improved topical
insecticide, which overcomes drawbacks of the prior art.
SUMMARY OF THE INVENTION
[0006] Generally speaking, in accordance with the invention, a
topical insecticide is provided which can be safe to use and avoids
many common deleterious side effects of conventional topical
insecticides. In one preferred embodiment of the invention, the
active ingredient of the insecticide formulation is an amine
derivative, having a nitro-methylene group, a nitroamino group or a
cyanoamino group, which can be formulated to have low toxicity and
excellent insecticidal activity. Active ingredients of insecticides
and their method of formation in accordance with the preferred
embodiments of the invention are discussed in U.S. Pat. Nos.
5,532,365 and 5,434,181, and U.S. application Ser. Nos. 10/242,550,
10/242,551 and 10/242,552 filed on Sep. 12, 2002, the contents of
which are incorporated herein by reference. One particularly
suitable insecticide is
1-{(tetrahydro-3-furanyl)methyl}-2-nitro-3-methyl- guanidine
(dinotefuran). Dinotefuran is an aldulticide that will kill adult
fleas.
[0007] In one preferred embodiment of the invention, the active
portion of the insecticide formulation comprises
(tetrahydro-3-furanyl)methylamine derivatives of following formula
(1). 1
[0008] Active ingredients and insecticides in accordance with
preferred embodiments of the invention are generally available as
crystals and solids. Therefore, they need to be dissolved or
otherwise put into a liquid form for use as topical spot products
on animals. Topical spot products are more advantageous if the
amount of liquid applied can be minimized. This must be balanced
with the need for appropriate dosage to achieve the desired
insecticidal effect. Therefore, it is desirable to use a solvent
that will allow the solubilization of a high concentration of
insecticide.
[0009] It is also desirable that the resulting formulation be
stable (i.e., no crystallization) when stored at 0.degree. F. and
40.degree. F. for 1 month, which is important because these
conditions can be met in commerce. The crystallization would reduce
the amount of insecticide in solution and reduce the efficacy of
the solution applied to the animal.
[0010] Phenyl methanol, is an alcohol, also known as benzyl
alcohol, and is a liquid, somewhat soluble in water. It is
routinely used in perfumes, flavors, photographic developers, dyes,
films and inks and has other uses. It was surprisingly discovered
that a relatively high concentration of the dinotefuran could be
solubilized in phenyl methanol.
[0011] Methoprene is an insecticide that acts as an insect growth
regulator that prevents flea eggs from hatching. It was
unexpectedly determined that methoprene can act as a solubility
enhancer for amine derivative insecticides such as dinotefuran,
discussed above. For example, the addition of methoprene to the
dinotefuran formulations with phenyl methanol allowed the
preparation of more highly concentrated solutions of dinotefuran
that do not crystallize at 0.degree. F.
[0012] In one aspect of the current invention, the dinotefuran is
dissolved in solvent containing methoprene to a concentration range
of 5-25%, more preferably 9-20% and most preferably about 12.5 to
19.2%, with 17.5% as a preferred example. All percentages, unless
otherwise evident, are on a weight basis.
[0013] The formulation can be applied as a topical drop about once
per month, preferably in the area between the shoulder blades and
the base of the skull to kill fleas and flea eggs for over a one
month period.
[0014] Accordingly, it is an object of the invention to provide an
improved topical insecticide, which overcomes drawbacks of the
prior art.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0015] The novel (tetrahydro-3-furanyl)methylamine derivatives of
the formula (1) have an excellent insecticidal activity even in the
absence of a pyridylmethyl group or a thiazolylmethyl group in
their molecular structure. According to the present invention,
there are provided (tetrahydro-3-furanyl)methylamine derivatives
represented by formula (1), where X.sub.1, X.sub.2, X.sub.3,
X.sub.4, X.sub.5, X.sub.6 and X.sub.7 represent each a hydrogen
atom or an alkyl group having from 1 to 4 carbon atoms; R.sub.1
represents a hydrogen atom, an alkyl group having from 1 to 5
carbon atoms, an alkenyl group having 3 carbon atoms, a benzyl
group, an alkoxyalkyl group having from 2 to 4 carbon atoms (in its
whole group), an alkyloxycarbonyl group having from 1 to 3 carbon
atoms, a phenoxy carbonyl group, an alkylcarbonyl group having from
1 to 6 carbon atoms, an alkenylcarbonyl group having from 2 to 3
carbon atoms, a cycloalkylcarbonyl group having from 3 to 6 carbon
atoms, a benzoyl group, a benzoyl group substituted by alkyl
group(s) having from 1 to 4 carbon atoms, a benzoyl group
substituted by halogen atom(s), a 2-furanylcarbonyl group or an
N,N-dimethylcarbamoyl group; R.sub.2 represents a hydrogen atom, an
amino group, a methyl group, an alkylamino group having from 1 to 5
carbon atoms, a di-substituted alkylamino group having from 2 to 5
carbon atoms (in its whole group), a 1-pyrrolidinyl group, an
alkenylamino group having 3 carbon atoms, an alkynylamino group
having 3 carbon atoms, a methoxyamino group, an alkoxyalkylamino
group having from 2 to 4 carbon atoms (in its whole group), a
methylthio group or --N(Y.sub.1)Y.sub.2 (where Y.sub.1 represents
an alkyloxycarbonyl group having from 1 to 3 carbon atoms, a
phenoxycarbonyl group, an alkylcarbonyl group having from 1 to 6
carbon atoms, an alkenylcarbonyl group having from 2 to 3 carbon
atoms, a cycloalkylcarbonyl group having from 3 to 6 carbon atoms,
a benzoyl group, a benzoyl group substituted by alkyl group(s)
having from 1 to 4 carbon atoms, a benzoyl group substituted by
halogen atom(s), a 2-furanylcarbonyl group, an
N,N-dimethylcarbamoyl group, a (tetrahydro-3-furanyl)methyl group
or a benzyl group, and Y.sub.2 represents a hydrogen atom or an
alkyl group having from 1 to 5 carbon atoms); and Z represents
.dbd.N--NO.sub.2, .dbd.CH--NO.sub.2 or .dbd.N--CN; insecticides
containing the derivatives as an effective ingredient; and
intermediates for producing the compounds of the formula (1)
represented by a formula (2): 2
[0016] where X.sub.1, X.sub.2, X.sub.3, X.sub.4, X.sub.5, X.sub.6
and X.sub.7 represent each a hydrogen atom or an alkyl group having
from 1 to 4 carbon atoms; R.sub.10 represents an alkyl group having
from 1 to 5 carbon atoms or a benzyl group; and R.sub.11 represents
an alkyl group having from 1 to 5 carbon atoms or a benzyl
group.
[0017] The novel (tetrahydro-3-furanyl)methylamine derivatives of
the formula (1) and formula (2) according to the invention are
excellent compounds having a high insecticidal power and broad
insecticidal spectrum. Further, agricultural chemicals containing
the novel (tetrahydro-3-furanyl)methylamine derivatives of the
formula (1) and (2) according to the invention have outstanding
characteristics as insecticides and hence are useful.
[0018] Specific examples of the alkyl group for X.sub.1, X.sub.2,
X.sub.3, X.sub.4, X.sub.5, X.sub.6 and X.sub.7 in the above
formulae (1) and (2) include a methyl group, an ethyl group, an
n-propyl group, an iso-propyl group, a tert-butyl group, and the
like, preferably a methyl group.
[0019] Specific examples of the alkyl group for R.sub.1 include a
methyl group, an ethyl group, an n-propyl group, an iso-propyl
group, an n-butyl group, an iso-butyl group, a sec-butyl group, a
tert-butyl group, an n-pentyl group, and the like.
[0020] Specific examples of the alkenyl group for R.sub.1 include a
1-propenyl group, a 2-propenyl group, and the like.
[0021] Specific examples of the alkoxyalkyl group for R.sub.1
include a methoxymethyl group, an ethoxymethyl group, an
n-propoxymethyl group, an iso-propoxymethyl group, a methoxyethyl
group, an ethoxyethyl group, and the like.
[0022] Specific examples of the alkyloxycarbonyl group for R.sub.1
include a methyloxycarbonyl group, an ethyloxycarbonyl group, an
n-propyloxycarbonyl group, an iso-propyloxycarbonyl group, and the
like.
[0023] Specific examples of the alkylcarbonyl group for R.sub.1
include a methylcarbonyl group, an ethylcarbonyl group, an
n-propylcarbonyl group, an iso-propylcarbonyl group, an
n-butylcarbonyl group, an iso-butylcarbonyl group, a
sec-butylcarbonyl group, a tert-butylcarbonyl group, an
n-pentylcarbonyl group, an n-hexylcarbonyl group, and the like.
[0024] Specific examples of the alkenylcarbonyl group for R1
include a vinylcarbonyl group, a 1-methylvinylcarbonyl group, and
the like.
[0025] Specific examples of the cycloalkylcarbonyl group for
R.sub.1 include a cyclopropylcarbonyl group, a cyclobutylcarbonyl
group, a cyclopentylcarbonyl group, a cyclohexylcarbonyl group, and
the like.
[0026] Specific examples of the benzoyl group substituted by alkyl
group(s) for R.sub.1 include a 2-methylbenzoyl group, a
3-methylbenzoyl group, a 4-methylbenzoyl group, a
4-tert-butylbenzoyl group, and the like.
[0027] Specific examples of the benzoyl group substituted by
halogen atom(s) for R.sub.1 include a 2-chlorobenzoyl group, a
3-chlorobenzoyl group, a 4-chlorobenzoyl group, a
3,4-dichloro-benzoyl group, a 4-fluorobenzoyl group, and the
like.
[0028] Although R.sub.1 can take various substituents as described
above, it is preferably a hydrogen atom, an alkylcarbonyl group
having from 1 to 4 carbon atoms or a cyclopropylcarbonyl group.
[0029] Specific examples of the alkylamino group for R.sub.2
include a methylamino group, an ethylamino group, an n-propyl-amino
group, an iso-propylamino group, an n-butylamino group, an
iso-butylamino group, a sec-butylamino group, a tert-butylamino
group, an n-pentylamino group, and the like, preferably a
methylamino group.
[0030] Specific examples of the di-substituted alkylamino group for
R.sub.2 include a dimethylamino group, a diethylamino group, an
N-methyl-N-ethylamino group, an N-methyl-N-n-propylamino group, an
N-methyl-N-n-butylamino group, and the like, preferably a
dimethylamino group.
[0031] Specific examples of the alkenylamino group for R.sub.2
include a 1-propenylamino group, a 2-propenylamino group, and the
like.
[0032] Specific examples of the alkynylamino group for R.sub.2
include a propargylamino group, and the like.
[0033] Specific examples of the alkoxyalkylamino group for R.sub.2
include a methoxymethylamino group, an ethoxymethylamino group, an
n-propoxymethylamino group, an iso-propoxymethylamino group, a
methoxyethylamino group, an ethoxyethylamino group, and the
like.
[0034] Specific examples of the alkyloxycarbonyl group denoted by
Y.sub.1 for R.sub.2 include a methyloxycarbonyl group, an
ethyloxy-carbonyl group, an n-propyloxycarbonyl group, an
iso-propyloxy-carbonyl group, and the like.
[0035] Specific examples of the alkylcarbonyl group denoted by
Y.sub.1 for R.sub.2 include a methylcarbonyl group, an
ethylcarbonyl group, an n-propylcarbonyl group, an
iso-propylcarbonyl group, an n-butylcarbonyl group, an
isobutylcarbonyl group, a sec-butylcarbonyl group, a
tertbutylcarbonyl group, an n-pentylcarbonyl group, an
n-hexylcarbonyl group, and the like, preferably a methylcarbonyl
group, an ethylcarbonyl group, an n-propylcarbonyl group, an
iso-propylcarbonyl group, an n-butylcarbonyl group, an
iso-butylcarbonyl group, a sec-butylcarbonyl group and a
tert-butylcarbonyl group.
[0036] Specific examples of the alkenylcarbonyl group denoted by
Y.sub.1 for R.sub.2 include a vinylcarbonyl group, a
1-methyl-vinylcarbonyl group, and the like.
[0037] Specific examples of the cycloalkylcarbonyl group denoted by
Y.sub.1 for R.sub.2 include a cyclopropylcarbonyl group, a
cyclobutylcarbonyl group, a cyclopentylcarbonyl group, a
cyclohexylcarbonyl group, and the like, preferably a
cyclopropyl-carbonyl group.
[0038] Specific examples of the benzoyl group substituted by alkyl
group(s) denoted by Y.sub.1 for R.sub.2 include a 2-methylbenzoyl
group, a 3-methylbenzoyl group, a 4-methylbenzoyl group, a
4-tert-butylbenzoyl group, and the like.
[0039] Specific examples of the benzoyl group substituted by
halogen atom(s) denoted by Y.sub.1 for R.sub.2 include a
2-chlorobenzoyl group, a 3-chlorobenzoyl group, a 4-chlorobenzoyl
group, a 3,4-dichlorobenzoyl group, a 4-fluoro benzoyl group, and
the like.
[0040] Specific examples of the alkyl group denoted by Y.sub.2 for
R.sub.2 include a methyl group, an ethyl group, an n-propyl group,
an iso-propyl group, an n-butyl group, an iso-butyl group, a
sec-butyl group, a tert-butyl group, an n-pentyl group, and the
like, preferably a methyl group.
[0041] In the formula (1), compounds in which R.sub.1 and Y.sub.1
are concurrently an alkylcarbonyl group having from 1 to 4 carbon
atoms or a cyclopropylcarbonyl group are preferred from the
viewpoint of both insecticidal activity and production method.
[0042] In the development of a formulation for use on animals,
there are several parameters that must be considered. These
are:
[0043] (a) Concentration high enough to minimize the volume of the
topical applied to the animal (one would not want to put 20 ml,
e.g., onto a small cat).
[0044] (b) The formulation should be stable for one month at
130.degree. F., 110.degree. F., 40.degree. F., room temperature and
0.degree. F. This helps ensure that the formulation remains stable
under the conditions that it could meet in commerce.
[0045] (c) Safe to use on the animal--particularly non-irritating
since the product is applied to the skin. Also safe if ingested by
the animal; ingestion can occur when cats groom themselves.
[0046] (d) Safe to use by the consumer.
[0047] (e) Efficacious in use--should kill greater than 90% of the
fleas up to 28 days.
[0048] (f) Efficacy would be reduced if crystallization occurred in
the package.
[0049] (g) Needs to be aesthetically pleasing--"no oily drop" on
the animal when applied.
[0050] (h) Fast drying to reduce the chance of the animal shaking
off the liquid thereby reducing efficacy.
[0051] (i) Microbiologically stable.
[0052] The above-referenced patents recognize different possible
solvents, but do not provide information on how to formulate
insecticide in a non-irritating manner. No examples were given in
which the compounds were used on animals. Additionally, in all of
the examples given the compounds were dissolved into solvents that
are undesirable to use on animals. Specifically, acetone, used in
all but one of the examples, is very irritating by both inhalation
and skin contact, due to de-fatting action on skin and mucous
membranes. It is also very irritating to the eyes. Accordingly,
there is a need to develop a different solvent for these compounds
that can be used on animals. The present formulation satisfies the
parameters detailed above.
[0053] In one aspect of the current invention, the dinotefuran is
dissolved in solvent containing methoprene to a concentration range
of 5-25%, more preferably 9-20% and most preferably about 12.5 to
19.2%, with 17.5% as a preferred example. All percentages, unless
otherwise evident, are on a weight basis. Methoprene is
advantageously included as over 0.1%, advantageously about 0.1 to
3%. Advantageous weight ratios of dinotefuran:methoprene range from
about 30:1 to 2.5:1, more preferably about 25:1 to 3:1.
[0054] The following examples are given for purposes of
illustration only and are not intended to be construed in a
limiting manner.
EXAMPLE 1
Preparation of
1-{(tetrahydro-3-furanyl)methyl}-2-nitro-3-methylguanidine
(Dinotefuran)
[0055] A mixture comprising 10.0 g of
(tetrahydro-3-furanyl)methanol, 29.5 g of trifluoromethanesulfonic
anhydride, 10.0 g of pyridine and 200 ml of dichloromethane was
stirred for an hour at room temperature. Water was poured into the
reaction solution to separate the organic layer, which was washed
with 1 N hydrochloric acid, water and a saturated saline solution,
dried, and concentrated to obtain 20 g of
3-tetrahydro-furanylmethyl triflate. 3.25 g of 60% sodium hydride
were added to 12.5 g of
1,5-dimethyl-2-nitroiminohexahydro-1,3,5-triazine and 60 ml of DMF
at room temperature, followed by stirring for an hour. 20.0 g of
the 3-tetrahydrofuranylmethyl triflate were added thereto, and the
mixture was stirred at 50.degree. C. for 2 hours. After cooling the
mixture to room temperature, 50 ml of 2N hydrochloric acid were
added thereto, followed by stirring at 50.degree. C. for 2 hours.
The resultant mixture was neutralized with sodium bicarbonate and
extracted with dichloromethane, and the extract was dried and
concentrated. The residue thus obtained was purified by silica gel
column chromatography (eluent:ethyl acetate/hexane=1/1) to obtain
7.8 g of 1-{(tetrahydro-3-furanyl)methyl}-2-nitro-3-methylguanidine
(dinotefuran).
EXAMPLE 2
Preparation of Insecticide Formulation Containing Dinotefuran,
Ethanol and Water
[0056] 5 g (i.e., 5.6% (weight/weight)) of dinotefuran was
dissolved into 100 ml of a mixture comprising 70% ethanol and 30%
water. The resulting mixture can be spot applied to companion
animals, such as dogs and cats and will kill fleas, ticks and other
insects.
EXAMPLE 3
Preparation of Insecticide Formulation Containing Dinotefuran and
Phenyl Methanol
[0057] 15 g (i.e., 12.5% (weight/weight)) of dinotefuran was
dissolved into 100 ml of phenyl methanol. The resulting solution
can be spot applied to companion animals, such as dogs and cats and
will kill fleas, ticks and other insects.
EXAMPLE 4
Preparation of Insecticide Formulation Containing Dinotefuran,
Pyriproxyfen and Phenyl Methanol
[0058] 20 g of dinotefuran was added to 100 ml phenyl methanol with
stirring until it dissolves. 3 g of pyriproxyfen was added to the
solution with stirring to produce a clear, homogeneous
solution.
EXAMPLE 5
Preparation of Insecticide Formulation Containing Dinotefuran
Pyriproxyfen and Phenyl Methanol
[0059] 25 g of dinotefuran was added to 100 ml phenyl methanol with
stirring until it dissolved. 1 g of pyriproxyfen was added to the
solution with stirring to produce a clear, homogeneous solution of
high insecticide concentration.
[0060] The resulting solution can be spot applied to companion
animals, such as dogs and cats and will kill fleas, ticks and other
insects.
EXAMPLE 6
Stability of Dinotefuran/Pyriproxyfen Formulations
[0061] Table 1 demonstrates that an approximate 50% increase in
concentration can be achieved for dinotefuran by including
pyriproxyfen at low levels in the formulation based on the
criterion of no crystal formation at 0.degree. F. during a 1 month
period.
1TABLE 1 Formulation Stability Studies (% are w/w) Dinotefuran
Pyriproxyfen Phenyl Methanol Stable 12.5 0 87.5 Yes 14.7 0 85.3 No*
15.7 2.4 81.9 Yes 15.9 0.8 83.3 Yes 19.2 0.8 80.0 Yes *Crystallizes
at 0.degree. F.
EXAMPLE 7
Preparation of Insecticide Formulation Containing Dinotefuran,
Methoprene and Phenyl Methanol
[0062] 20 g of dinotefuran was added to 100 ml phenyl methanol with
stirring until it dissolved. 1 g of methoprene was added to the
solution with stirring to produce a clear, homogeneous solution of
high insecticide concentration.
EXAMPLE 8
Preparation of Insecticide Formulation Containing Dinotefuran,
Methoprene and Phenyl Methanol
[0063] 18 g of dinotefuran was added to 100 ml phenyl methanol with
stirring until it dissolved. 1 g of methoprene was added to the
solution with stirring to produce a clear, homogeneous solution of
high insecticide concentration.
EXAMPLE 9
Preparation of Insecticide Formulation Containing Dinotefuran,
Methoprene and Phenyl Methanol
[0064] 16 g of dinotefuran was added to 100 ml phenyl methanol with
stirring until it dissolved. 1 g of methoprene was added to the
solution with stirring to produce a clear, homogeneous solution of
high insecticide concentration.
EXAMPLE 10
Stability of Dinotefuran/Methoprene Formulations
[0065]
2TABLE 2 Formulation Stability Studies (% are w/w) Dinotefuran
Methoprene Phenyl Methanol Stable 12.5 0 87.5 Yes 14.7 0 85.3 No*
19.2 0.8 80.0 No* 18.5 0.8 80.7 Yes 17.5 0.8 81.7 Yes 16.0 0.8 83.2
Yes 14.6 0.8 84.6 Yes 12.9 3.2 83.9 Yes 12.1 4.0 83.9 Yes
*Crystallizes at 0.degree. F.
[0066] It has been determined that the concentration of dinotefuran
can be increased up to 50% and more by including methoprene, even
at low levels of about 0.8% and below, compared to a similar
formulation without methoprene. Also, inclusion of methoprene up to
and over 4% are stable. Typically, dinotefuran concentration of
over about 8% will crystallize at 0.degree. F. within a few
days.
EXAMPLE 11
In Vivo Activity of a Flea Dermal Treatment Against the Cat Flea
(Ctenocephalides felis) on Cats
[0067] Eighteen cats were separated into three groups each
containing 6 cats. Group 1 (6 cats each weighing 9 lbs. or less)
remained untreated as Non-Treated Controls. Group 2 (6 cats each
over 9 lbs.) were treated with 3.4 ml of the dinotefuran
insecticide formulation (5.71% w/w). Group 3 (6 cats each weighing
9 lbs. or less) were treated with 1.5 ml of the dinotefuran
insecticide formulation (5.71% w/w).
[0068] Approximately 18 hours prior to treatment the cats were
infested with 100 cat fleas (Ctenocephalides felis) which were
applied to the animal's back. Cats in Groups 2 and 3 were then
treated with the indicated volume of insecticide by dispensing the
liquid at skin level between the shoulder blades. Flea counts were
taken at day 1 (i.e., 24 hours post-treatment), day 8, day 15, day
22 and day 29. Cats were re-infested with 100 fleas on days 7, 14,
21, and 28. To determine the efficacy of the dermal treatment, the
number of fleas found on treated cats was compared to the number of
fleas found on untreated cats. Percent reduction was determined as
follows and the results are summarized in Table 2: 1 Mean Number of
fleas on Untreated Cats - Mean Number of fleas on Treated Cats Mean
Number of fleas on Untreated Cats .times. 100 %
[0069] As shown in Table 2 the results demonstrate that the dosages
used on Groups 2 and 3 are both effective at reducing the number of
adult fleas on cats through at least 29 days and thus are effective
as a one month dermal treatment.
3TABLE 3 Controlled Percent Reduction in Flea Population Day 1 Day
8 Day 15 Day 22 Day 29 Control 0 0 0 0 0 Group 1 Group 2 100 100 99
99 96 Group 3 100 98 95 95 91
[0070] It will thus be seen that the objects set forth above, among
those made apparent from the preceding description, are efficiently
attained and, since certain changes may be made in carrying out the
above method and in the composition set forth without departing
from the spirit and scope of the invention, it is intended that all
matter contained in the above description shall be interpreted as
illustrative and not in a limiting sense.
[0071] It is also to be understood that the following claims are
intended to cover all of the generic and specific features of the
invention herein described and all statements of the scope of the
invention which, as a matter of language, might be said to fall
therebetween.
[0072] Particularly it is to be understood that in said claims,
ingredients or compounds recited in the singular are intended to
include compatible mixtures of such ingredients wherever the sense
permits.
* * * * *